CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles

Eur J Immunol. 1999 May;29(5):1610-6. doi: 10.1002/(SICI)1521-4141(199905)29:05<1610::AID-IMMU1610>3.0.CO;2-8.

Abstract

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DC) express OX40-ligand (OX40L) as has been reported in humans. To understand how OX40 ligation affects differentiation of CD4 T cells at the time of priming, we constitutively expressed OX40L on DC using the DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was to a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately immunized did not show marked CD4 T cell accumulation. The increased numbers of CD4+ CD62low cells in transgenic mice suggest that it is activated CD4 T cells that accumulate within B cell follicles. These data are consistent with the notion that physiological engagement of OX40 (CD134) on activated CD4 T cells either initiates their migration into or causes them to be retained in B follicles. In contrast, LPS-treated CD did not up-regulate OX40L expression. This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology*
  • CD40 Antigens / immunology
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Dendritic Cells / immunology*
  • Female
  • Immunophenotyping
  • Integrin alphaXbeta2 / genetics
  • Integrin alphaXbeta2 / immunology
  • Ligands
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Immunologic / immunology*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology*
  • Tumor Necrosis Factors
  • Vaccination

Substances

  • CD40 Antigens
  • Integrin alphaXbeta2
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors